Article

Association of a TRAF1 and a STAT4 gene polymorphism with increased risk for rheumatoid arthritis in a genetically homogeneous population

Department of Medicine, University of Crete, and Department of Rheumatology, Clinical Immunology and Allergy, University Hospital of Heraklion, Heraklion, Greece.
Human Immunology (Impact Factor: 2.28). 08/2008; 69(9):567-71. DOI: 10.1016/j.humimm.2008.06.006
Source: PubMed

ABSTRACT Rheumatoid arthritis (RA) is a multifactorial disease that is increasing in incidence worldwide. It is associated with a complex mode of inheritance, with many genes being involved in the development and progression of the disease. Genome-wide association studies in different populations have recently revealed a significant association between a TRAF1/C5 and a STAT4 polymorphism and the development of RA. In the present study we performed a case-control study in the population of the island of Crete, Greece, aiming to replicate the former findings in a genetically homogeneous cohort of patients. We found that mutated allele A or genotypes A/A and G/A of the TRAF1/C5 rs10818488 SNP were more common in individuals with RA than in control individuals (odds ratio [OR]=1.7, 95% confidence interval [CI]=1.35-2.15, and OR=2.22, 95% CI=1.61-3.05, respectively). Similarly, mutated allele T or genotypes T/T and G/T of the STAT4 rs7574865 SNP were also associated with susceptibility to RA (OR=1.9, 95% CI=1.46-2.50, and OR=2.37, 95% CI 1.73-2.25, respectively). Thus, we conclude that mutant alleles or genotypes of both polymorphisms examined are associated with the development of RA in our population.

0 Followers
 · 
138 Views
  • Source
    • "IMBIO-51310; No. of Pages 13 6 R. Elshazli, A. Settin / Immunobiology xxx (2015) xxx–xxx Fig. 2. Odds ratios and 95% confidence intervals (CIs) of individual studies and of pooled data for the association between the T allele of PTPN22 polymorphism and RA. 2012; Palomino-Morales et al., 2010); and genotype frequencies that are not in HWE in control groups (Zervou et al., 2008) (Table 3). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The genes encoding protein tyrosine phosphatase non-receptor type 22 (PTPN22) and signal transducer and activator of transcription 4 (STAT4) have been reported to be associated with RA in several ethnic populations. This work aims to assess the association between PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility through an updated meta-analysis of available case-control studies. A literature search of all relevant studies published from January 2007 up to December 2014 was conducted using Pubmed and Science Direct databases. The observed studies that were related to an association between PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility were identified. Meta-analyis of the pooled and stratified data was done and assessed using varied genetic models. Thirty-seven case-control studies with a total of 47 comparisons (29 for PTPN22 rs2476601 polymorphism and 18 for STAT4 rs7574865 polymorphism) met our inclusion criteria. The meta-analysis showed an association between PTPN22 T allele, CT+TT and TT genotypes with RA susceptibility. Furthermore, The meta-analysis showed an association between STAT4 T allele, GT+TT and TT genotypes with RA susceptibility. Stratification of RA patients according to ethnic groups showed that PTPN22 T allele, CT+TT genotypes, STAT4 T allele and STAT4 GT+TT were significantly associated with RA in European, Asian, African subjects, while PTPN22 TT genotype was significantly associated with RA in European but not in Asian and African subjects and STAT4 TT genotype was significantly associated with RA in European and Asian but not in African subject. A subgroup analysis according to the presence or absence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies revealed that the association between PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility may not be dependent on RF and anti-CCP antibodies. Our meta-analysis demonstrated that PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms confers susceptibility to RA in total subjects and in major ethnic groups. The association may not be dependent on RF and anti-CCP antibodies. Copyright © 2015 Elsevier GmbH. All rights reserved.
    Immunobiology 04/2015; DOI:10.1016/j.imbio.2015.04.003 · 3.18 Impact Factor
  • Source
    • "Since Th1 and Th17 lineages are crucial effectors in chronic inflammatory disorders, STAT4 gene may play an important role in the pathogenesis of autoimmune diseases. To date, the SNP rs7574865 in STAT4 gene has been reported to be associated with an increased risk for diverse complex autoimmune diseases in different ethnic populations, such as RA [9] [10] [11] [12] [13]. Knowing that the allelic frequencies of genes often differ substantially between populations; we were interested to test the association http://dx.doi.org/10.1016/j.humimm.2014.06.013 0198-8859/Ó 2014 American Society for Histocompatibility and Immunogenetics. "
    [Show abstract] [Hide abstract]
    ABSTRACT: a b s t r a c t Background: The gene encoding signal transducer and activator of transcription 4 (STAT4) has been reported to be associated with rheumatoid arthritis (RA) in several populations. This work aimed at asses-sing the association of STAT4 G>T gene polymorphism with the susceptibility, activity and functional dis-ability of RA in Egyptian subjects. Subjects and methods: This study included 112 unrelated RA Egyptian patients who were compared to 122 healthy unrelated individuals taken from the same locality. For all subjects, DNA was genotyped for STAT4 G>T (rs7574865) polymorphism using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). Results: Cases showed a significantly higher frequency of the STAT4 T allele carriage (GT+TT genotypes) compared to controls (51.8% vs. 31.1%, OR = 2.37, 95% CI = 1.39–4.05, p = 0.001). Also the frequency of the STAT4 T allele was significantly higher among cases compared to controls (30.4% vs. 16.8%, OR = 2.16, 95% CI = 1.39–3.35, p = 0.001). Cases positive to the STAT4 T allele (GT+TT genotypes) showed no significant difference compared to those with the GG genotype regarding their clinical and immune parameters. Nonetheless, they showed a more functional disability presented in their significantly higher health assessment questionnaire (HAQ) score (p = 0.02). Conclusions: This study gives an extra evidence to the association of the STAT4 T allele with the suscept-ibility and functional disability of RA.
    Human Immunology 06/2014; 75(8). DOI:10.1016/j.humimm.2014.06.013 · 2.28 Impact Factor
  • Source
    • "The odds ratio in the initial white North American sample sets was 1.32 (1620 cases and 2635 controls) [46] decreasing to 1.15 in a larger study (>5000 RA cases and ∼6000 controls) [47]—an example of the phenomenon known as the " winner's curse " or " regression to the mean " in which effect sizes are often over-estimated in original studies. In contrast to the W620 RA-associated variant in PTPN22, rs7574865 is associated with RA in other ethnic groups including Asians [49] [50], Central Americans [51] and an isolated Greek population [52]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Talk of numerous genetic risk factors for rheumatoid arthritis (RA) and psoriasis has been percolating for years, but with the exception of the human leukocyte antigen (HLA) region, none have been definitively identified. Recently the results of multiple, well powered, genetic case–control studies have begun to appear providing convincing statistical evidence for at least ten non-HLA related risk genes or loci (C5/TRAF1, CD40, CTLA4, KIF5A/PIP4K2C, MMEL1/TNFRSF14, PADI4, PRKCQ, PTPN22, STAT4, and TNFAIP3/OLIG3) for RA and six (IL12B, IL13, IL23R, STAT2/IL23A, TNFAIP3, and TNIP1) for psoriasis. These initial, novel findings are beginning to shed light on the molecular pathways pertinent to the individual diseases and highlight the pleiotropic effects of several risk factors as well as the allelic heterogeneity underlying susceptibility to these and other autoimmune diseases.
    Seminars in Immunology 12/2009; 21(6-21):318-327. DOI:10.1016/j.smim.2009.04.002 · 6.12 Impact Factor
Show more

Preview

Download
7 Downloads
Available from